In recent years, bicarbonate dialysates have come to be used more frequently in hemodialysis in favor of acetic acid-containing dialysates because bicarbonate dialysates impose less burden on a patient's body as compared to acetic acid-containing ones. However, it is difficult to prepare a one-pack type bicarbonate-containing preparation for dialysis due to the reactions between bicarbonate ions and magnesium or calcium ions contained therein as electrolytes for producing insoluble compounds (metal bicarbonate salts such as calcium bicarbonate and magnesium bicarbonate).
Therefore, a typical bicarbonate-containing preparation for dialysis consists of two components of a concentrate liquid agent “A” containing electrolytes such as calcium and magnesium ions, as well as glucose and a pH adjusting agent if necessary, and a powdery agent “B” containing sodium hydrogencarbonate of bicarbonate ions.
However, abovementioned concentrate liquid agent “A” is typically packed in a polyethylene bag in the amount between about 5 L and 15 L. The weight and transportation costs of the bag, storage space in hospital and disposal of waste fluid are a great burden.
As a solution to above problems, it has been suggested providing agent “A” in powder, and powdery agent “A” products are now commercially available (Patent literature 1). Such an agent “A” is typically a powdery or granular preparation made from a mixture of powdery ingredients, which are granulated, if necessary with a binder solution, subsequently dried and sieved.
In conventional powdery or granular preparations for dialysis, however, particles of ingredients are typically fine, and dust rises when the powders or granules are put into a dissolving machine. Additionally, conventional powdery or granular preparations for dialysis often have a strong smell caused by acetic acid contained therein as a pH adjusting agent. The above problems deteriorate working environment in production sites and healthcare sites.
In addition, acetic acid, which is contained slightly in conventional preparations for dialysis as a pH adjusting agent, practically does not exist in the living body by nature (0.1 mEq/L or less). Further, it has recently been recognized problematic that acetic acid may cause undesirable clinical symptoms such as headache or blood pressure reduction during a dialysis treatment.
In other words, it was considered not problematic to add a slight amount of acetic acid like between about 8 and 12 mEq/L in a bicarbonate-containing preparation for dialysis as a pH adjusting agent. However, prolongation of dialysis treatment and improvements in dialyzer's performance in recent years have resulted in excessively loading acetic acid contained in a dialysate on a patient's body and causing adverse effects on cardiovascular system. In parallel, adverse effects of acetic acid such as acetate intolerance have been recognized more severe than ever thought. To solve these problems, acetate-free preparations for dialysis containing solid organic acids such as citric acid have been developed (Patent literatures 2 and 3).
Solid organic acids such as citric acid contained in a preparation for dialysis as pH adjusting agents cause decomposition of glucose due to their strong acidic nature when stored for a long time under a condition that allows direct contact between solid organic acids and glucose. The decomposition of glucose produces decomposition products such as 5-hydroxymethyl furfural (5-HMF), and such decomposition of glucose increases under a condition of overhydration.
When acetic acid and acetate salts (sodium acetate) are used as conventional pH adjusting agents, acetic acid quickly permeates solid sodium acetate to adjust a pH ranging between 4 and 5. This prevents direct contact between acetic acid and glucose and, therefore, the decomposition of glucose is not a problem. However, the decomposition of glucose becomes a crucial problem when non-acetate solid organic acids are used as pH adjusting agents. Therefore, there is a need for development of a powdery or granular preparation for dialysis wherein the decomposition of glucose is suppressed.    [Patent literature 1] Japanese Patent Examined Publication No. Sho 57-88116    [Patent literature 2] Japanese Laid-open Patent Publication No. Hei 9-301875    [Patent literature 3] Japanese Laid-open Patent Publication No. 2005-330241